Pediatric Blood & Cancer最新文献

Background: The last major North American cooperative group clinical trial for relapsed favorable-histology Wilms tumor (FHWT) was completed in 2002. The outcomes of patients with relapsed Wilms tumor subsequently treated outside of clinical trials are unknown. The aim of this study was to assess the efficacy and toxicity of salvage therapies used for patients with FHWT suffering first relapse.

Methods: We conducted a retrospective chart review of patients treated for first relapse of FHWT at six large North American institutions from January 2002 through August 2018.

Results: Ninety-four patients were identified. Thirty-six patients were classified as standard-risk relapse (SRR), 49 patients as high-risk relapse (HRR), and seven patients as very high-risk relapse (VHRR). Two patients were unable to be classified. Twenty-one patients with SRR were treated with Regimen I. The 4-year event-free survival (EFS) and overall survival (OS) for SRR were 82.4% and 93.3%, respectively, with median follow-up of 72 months. Twenty-eight HRR/VHRR patients were treated with ICE therapy, while 13 received National Wilms Tumor Study (5th) (NWTS-5) Stratum C. No patient completed protocol therapy per Stratum C; median maintenance cycles administered were two cycles. The 4-year EFS and OS for HRR/VHRR were 32.6% and 58.3%, respectively, with median follow-up of 33 months.

Conclusions: Outcomes for all strata of relapsed WT patients treated in a non-clinical setting appear to have similar outcomes to historical cohorts treated on NWTS-5. Improved strategies are urgently needed for HRR and VHRR relapses.

Background: Delayed excretion of high-dose methotrexate (HD-MTX) in pediatric acute lymphoblastic leukemia (ALL) can result in significant morbidity. While methotrexate is primarily renally excreted, HD-MTX may overwhelm renal excretion and increase reliance on fecal elimination. This study evaluated the association between laxative use for constipation and delayed excretion of HD-MTX.

Methods: This multisite chart review included pediatric patients with ALL (2010-2020) who received HD-MTX (5 g/m²). Delayed excretion was defined as a serum MTX concentration greater than 0.4 µM at Hour 48. We identified use of laxative medications after each HD-MTX infusion, with receipt of two or more doses considered a proxy for constipation. Multilevel logistic regression models evaluated associations between clinical factors and delayed HD-MTX excretion to account for multiple MTX cycles per individual.

Results: A total of 533 eligible patients received 1875 HD-MTX infusions. Patients were mostly male (59.8%), Hispanic (56.7%), with a median age of 9.5 years. Delayed excretion was observed following 42.7% of HD-MTX infusions, and patients received two or more laxative doses during 19.9% of infusions. Independent of other factors, individuals who received two or more laxative doses were nearly 60% (odds ratio 1.58; 95% confidence interval: 1.19-2.09; p = .002) more likely to experience delayed excretion compared to those receiving fewer than two laxative doses.

Conclusion: Receipt of at least two laxative doses was independently associated with delayed methotrexate excretion in pediatric patients with ALL. Future prospective studies are needed to confirm the secondary effects of constipation and confirm the association with constipation and identify clinical benefits that optimize drug excretion.

Background: The increased accessibility and utilization of molecular testing including next-generation sequencing (NGS) has impacted the practice of pediatric pathology, with diagnostic, prognostic, and therapeutic implications for our patients. This survey is the first to describe the utilization of molecular testing in the routine practice of pediatric pathology for the care of children with known or suspected solid tumors.

Procedure: The Society for Pediatric Pathology Practice Committee distributed a survey to our membership asking 25 questions about training, practice setting, molecular ordering practices, and barriers to testing.

Results: Seventy-five pathologists responded to the survey. The survey provides valuable insight into the current use of molecular testing for the care of children with known or suspected solid tumors. Most respondents reported that they are increasingly using a variety of molecular techniques, with increased use over time, and that NGS is useful.

Conclusions: These results highlight a variety of barriers to molecular testing, including cost, insurance coverage, turnaround time, limitations of available assays (including limited coverage of pediatric-specific alterations), and difficulty in determining the most appropriate test to order. These data may be useful in supporting pediatric pathologists in their practice.

Background: Childhood cancer survivors (CCS) have a 50% higher risk of diabetes mellitus (DM) compared with the general population. Interventions in survivors with prediabetes (fasting glucose 100-125 mg/dL or hemoglobin A1c 5.7%-6.4%) may mitigate the development of DM and its attendant morbidity, but there is limited information on the feasibility of secondary prevention in this setting.

Methods: This 6-week pilot feasibility 1:1 randomized controlled trial enrolled 20 CCS on a structured telehealth exercise program ± nicotinamide riboside (NR), a nicotinamide adenine dinucleotide precursor. Feasibility metrics were: (1) ≥50% of eligible CCS enrolled onto study; (2) ≥70% of participants completed baseline and end-of-study assessments; (3) ≥70% compliance with exercise and NR. Secondary endpoints included changes in biomarkers associated with glucose homeostasis and muscle health.

Results: Median age (years) at cancer diagnosis was 16.5 (range, 1.5-21.5) and 35.5 (range, 18.0-67.0) at study enrollment. Enrollment rate was 87%, and 85% of participants completed baseline and end-of-study assessments. The mean percentage of exercise sessions completed was 86.6%; NR compliance was > 90%. There were no severe adverse events attributable to study interventions. Secondary endpoints were not significantly different between study arms at study completion. Myostatin decrease was observed in participants who completed a higher median number of exercise sessions and was associated with decreased intramuscular adipose tissue and increased lower extremity muscle cross-sectional area.

Conclusions: A telehealth exercise intervention ± NR supplementation was feasible in CCS with prediabetes. Future studies in larger cohorts may be needed to evaluate their beneficial effects on muscle health and DM risk among CCS.